Previous work from this laboratory showed that the oxidation of branched chain amino acids (leucine, isoleucine and valine) by skeletal and heart muscle of the rat is under metabolic, nutritional and hormonal regulation. The studies are being extended to other tissues which actively oxidize branched chain amino acids e.g. nerves and blood vessels. Studies in progress indicate that muscles and nerves of diabetic rats oxidize leucine faster than controls, and this can be reversed in vitro by insulin in the presence of glucose. The mode of action of insulin on this process will be studied, as well as that of other hormones (epinephrine, cortisol, glucagon and GH). Studies concerning the role of leucine and isoleucine as lipid precursors in different tissues will be continued in control and diabetic rats. Accelerated branched chain amino acid oxidation by muscles is generally associated with the catabolic state; we will continue current investigations which suggest that the concentration of leucine in muscle cells or a compartment thereof may modulate the rate of protein turnover in muscles. Studies concerning the cellular mechanisms which regulate the oxidation of branched chain amino and alpha-keto acids will be continued.